Vascular disorders preceding diagnosis of cancer: distinguishing the causal relationship based on Bradford-Hill guidelines

The literature investigating the association between vascular disorders and malignant neoplasms does not comprehensively review the full spectrum of vascular disorders associated with cancer, or provide proof that cancer is an etiologic factor in the development of these disorders. This paper investigates the causal role of cancer in the pathogenesis of vascular disorders, based on the Bradford-Hill criteria of causation. The Medline database was searched for articles on vascular disorders preceding the diagnosis of cancer (VDPCD). Included in the analysis were vascular disorders caused either by direct tumoral involvement of vessels or by paraneoplastic mechanisms. Vascular disorders caused by adverse reactions to anticancer therapy were excluded from analysis. Seven categories of VDPCDs were recognized: venous thromboembolism, arterial thrombosis and embolism, nonbacterial thrombotic endocarditis, migratory superficial thrombophlebitis, vasculitis, thrombotic microangiopathy, and leukothrombosis. To establish causality of the association between VDPCDs and malignancy, the degree of fulfillment of the Bradford-Hill criteria was assessed. A strong association was found in the literature between venous thromboembolism and cancer (OR 2.3-14.9 and SIR 1.3-4.4). Consistency and temporality of the association were confirmed in all VDPCD variants. Seven Bradford-Hill criteria were fulfilled for cancer associated with venous thromboembolism, six criteria for superficial phlebitis and cancer, and five criteria for each of the other VDPCDs. In conclusion, these data support the causal role of cancer in the pathogenesis of all seven categories of VDPCDs. Recognition of such a causal link between cancer and various vascular disorders may promote an earlier cancer diagnosis.     

Acute idiopathic scrotal edema in children--revisited

Background: Acute idiopathic scrotal edema (AISE), a self-limiting acute scrotal edema and erythema that resolves without sequela, was first reported by Qvist in 1956. Methods: Thirty eight patients with AISE seen in the authors' department over the last 10 years were reviewed, comprising 44 episodes, most occurring in children under 10 years of age. The average age at presentation was 6.2 years. No past history of allergy was elicited. Results: Unilateral involvement predominated (90.1%). None of the patients was found to have a primary source of scrotal, perineal, or perianal infection. Scrotal discomfort; scrotal, perineal, and inguinal swelling; and erythema were the most common findings. Laboratory and ancillary examination findings were normal, except for the occasional eosinophilia. Characteristic ultrasonographic findings, such as marked thickening of the scrotal wall, with heterogeneous and edematous appearance, increased peritesticular blood flow, mild reactive hydrocele, and enlarged inguinal lymph nodes were found. Treatment was conservative in 92.1% of the patients. Resolution of all episodes occurred within 1 to 4 days. Recurrent episodes were observed in 4 patients (10 episodes), which were clinically more severe than the original episode. Conclusion: Clinical experience, good judgment, and color Doppler ultrasound scan can reliably identify those children with an acute scrotum who require exploration and spare those with AISE, where surgery is not indicated. J Pediatr Surg 37:1200-1202.     

Linkage of boronated polylysine to glycoside moieties of polyclonal antibody; boronated antibodies as potential delivery agents for neutron capture therapy

Among the ways to deliver comparatively large amounts of boron to cells in vitro for boron neutron capture studies is the linkage of a boronated macromolecule such as polylysine to an antibody. In order to reduce interference with immunoreactivity, boronated polylysine (BPL) was linked to oligosaccharide moieties on the IgG molecule distant from the antibody combining sites. The resultant bioconjugate was chromatographically separated from free BPL and unconjugated antibody using a Sephacryl S300 column. The total measured boron per BPL-IgG conjugate, determined by direct current plasma atomic emission spectroscopy, was estimated to be approximately 6 x 10(3) atoms. This, together with molecular weight estimations, indicated conjugation of about 3 polylysines to each IgG molecule. Immunoreactivity of the conjugate was found to be the same as that of the unconjugated polyclonal antibody. This was based on its concentration dependent interference with immunometric reactions for an antigen (TSH), whereas heat inactivated or non-specific antibody had no such inhibitory effects. The results support the hypothesis that the binding affinity of the conjugate for antigen was preserved after its linkage to BPL under the conditions described. The methodology described in this report may have applicability for the preparation of boronated antibodies as delivery agents for BNCT.     

RNASEL mutation screening and association study in Ashkenazi and non-Ashkenazi prostate cancer patients.

Epidemiologic and genetic studies support the considerable effect of heritable factors on prostate tumorigenesis, although to date, no unequivocal susceptibility gene has been identified. The extensive study of RNASEL in prostate cancer patients worldwide has yielded conflicting results. We reevaluated the role of the RNASEL 471delAAAG Ashkenazi founder mutation in 1,642 Ashkenazi patients with prostate, bladder, breast/ovarian, and colon cancers; Ashkenazi controls; and in non-Ashkenazi prostate cancer patients and controls. The entire RNASEL coding sequence was also screened using denaturing high-performance liquid chromatography and multiplex ligation-dependent probe amplification for possible sequence variations or copy number changes in a population of prostate cancer patients. The 471delAAAG mutation was detected in 2.4% of the Ashkenazi prostate cancer patients; in 1.9% of patients with bladder, breast/ovarian, and colon cancers; and in 2.0% of the Ashkenazi controls. Seven additional variants were detected in RNASEL, including a novel potentially pathogenic splice site mutation, IVS5+1delG, although none were associated with increased prostate cancer risk. Multiplex ligation-dependent probe amplification analysis showed two RNASEL gene copies in all 300 prostate cancer patients tested. We estimated that the RNASEL 471delAAAG founder mutation, which was detected in 2% of the Ashkenazi Jews, originated between the 2nd and 5th centuries A.D., compared with the less frequent (1%) BRCA1 185delAG founder mutation, which originated hundreds of years earlier. Taken together, our analysis does not support a role for the RNASEL 471delAAAG Ashkenazi mutation nor for the other alterations detected in RNASEL in prostate cancer risk in Jewish men.     

Host feeding of mosquitoes (Diptera: Culicidae) associated with the recurrence of Rift Valley fever in Egypt

In 1993, Rift Valley fever (RVF) virus reappeared in Egypt. We determined the prevalence and feeding patterns of mosquitoes in 5 villages where the virus was active. Of 10 species recovered, Aedes caspius (Pallas), Culex pipiens L., Cx. antennatus (Becker), and Cx. perexiguus Theobald constituted 99% of > 35,000 mosquitoes captured in dry ice-baited CDC light traps. Ae. caspius was most prevalent, except at Nag' El Hagar where it was replaced by Cx. perexiguus. Cx. pipiens ranked 2nd, except at Nag' El Ghuneimiya, where it was replaced by Cx. antennatus. Most blood meals analyzed by an enzyme-linked immunosorbent assay reacted to > or = 1 antiserum. Cx. pipiens was mainly anthropophagic, and therefore may have been the main vector of RVF virus among humans. Ae. caspius feeds were chiefly from humans, bovines, and equines. Cx. antennatus and Cx. perexiguus fed generally on bovines. Mixed blood meals from humans and RVF virus susceptible animals were identified in the predominant mosquitoes. Prevalence and host selection, as well as predicted probability for a blood meal being interrupted, indicated that Ae. caspius may have served as a bridge vector between humans and bovines in 4 of the villages. Cx. perexiguus may have played this role at Nag' El Hagar. Because potential vectors are abundant, susceptible domestic animals are associated closely with humans, and surveillance of imported livestock is not systematic, we conclude that RVF virus sporadically will recur in Egypt.     

Human DNA topoisomerase II-alpha expression in laparoscopically treated renal cell carcinoma

To investigate whether the expression of Topoisomerase II-alpha (TII-alpha) can serve as a prognostic factor in renal cell carcinoma (RCC), histological sections from 27 renal tumors were stained immunohistochemically for TII-alpha expression. The percentage of positive cells in the area of greatest staining was recorded as the TII-alpha index. TII-alpha nuclear staining was positive in all the samples except one. The mean TII-alpha index was 12.5 for grade 1, 44 for grade 2 and 113 for grade 3 tumors. The mean TII-alpha index was 22.3 in tumors which did not recur and 81 for tumors which recurred during the follow-up period. In this study, a higher TII-alpha index correlated with more aggressive tumor behaviour. However, a large cohort of patients should be assessed before drawing definitive conclusions.